TESTING FOR PROTEINS WITH
POLYGLUTAMINE EXPANSIONS
IN THE STANLEY FOUNDATION BRAIN COLLECTION
Alan H. Sharp*, Chuanyi
Zhang, Scott Maas, Jesse Mez and Christopher a. Ross
Johns Hopkins University, Department of Psychiatry and Behavioral
Sciences, Baltimore, MD.
Susceptibilities to schizophrenia and
bipolar disorder are thought to be inherited and these diseases
share certain features with inherited progressive
neurodegenerative diseases known to be caused by expansions of
polyglutamine tracts in proteins. For example, there is evidence
of anticipation in schizophrenia and bipolar disorder as in known
polyglutamine-expansion diseases. In schizophrenia, there is
evidence of overall atrophy of the brain and in some cases of a
progressive course. Therefore, we are screening the Stanley Brain
Collection and tissue from other sources for proteins with
polyglutamine expansions to determine whether such proteins may
contribute to susceptibility to schizophrenia and bipolar
disorder. We are using two approaches to screen for polyglutamine
expansions. First, expansions can be detected on Western blots of
brain tissue using the monoclonal antibody 1C2. This antibody
selectively recognizes tracts of about 20 or more glutamines, a
threshold which corresponds well with the threshold for disease
in most of the polyglutamine diseases. A second approach is to
detect, by immunohistochemistry, intranuclear inclusions which
are now considered a hallmark of polyglutamine expansion
diseases. Intranuclear inclusions can be detected with the
anti-polyglutamine antibody 1C2 or with anti-ubiquitin
antibodies. This work will test the hypothesis that proteins with
polyglutamine expansions may contribute to susceptibility to
schizophrenia and bipolar disorder.